RESUMEN
In the last decades, increasing success rates are being obtained in the chemotherapy of pediatric leukemia and lymphoma. However, the cornerstone of this treatment is still formed by a reduced number of drugs with a highly toxic profile. In particular, central nervous system complications remain a challenging clinical problem, requiring rapid detection and prompt treatment to limit permanent damage. Furthermore, clinicians are often challenged to discriminate between CNS involvement by the disease, toxicity of drugs or infections. This clinically oriented review will help recognize and handle the main neurologic adverse effects induced by chemotherapy in pediatric patients with lymphoblastic leukemia/lymphoma. Different clinical entities and putative drugs involved are discussed in each chapter, with clinical cases illustrating the most relevant and challenging events. In addition, specific clinical-radiological patterns of some of these neurologic events are detailed. Finally, the role of pharmacogenetics, with special focus on those polymorphisms that could help explain the occurrence of neurotoxicity, is also discussed.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades del Sistema Nervioso Central/inducido químicamente , Síndromes de Neurotoxicidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Farmacogenética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/etiologíaRESUMEN
No disponible
Asunto(s)
Humanos , Epilepsia del Lóbulo Frontal/diagnóstico , Epilepsias Parciales/diagnóstico , Diagnóstico DiferencialRESUMEN
Subacute methotrexate neurotoxicity (MTX-NT) may occur days to weeks after systemic or intrathecal (IT) MTX administration and is often manifest by stroke-like symptoms. The pathogenesis of MTX-NT has mainly been associated with cerebral folate homeostasis, but the specific mechanism leading to the development of this complication is mostly unknown and is likely to be multifactorial. Most of studies aimed to determine putative genetic determinants of this syndrome have been focused on the methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism (SNP). However, there are other functional polymorphisms that have also been identified in enzymes and transporters related to MTX and folate homeostasis. In this context, we carried out an extensive genetic analysis through the screening of 21 SNPs in 11 relevant genes in a five-year-old girl with acute lymphoblastic leukemia (ALL) who developed MTX-NT. The analysis revealed the presence of numerous genetic variants that may have accounted for the neurotoxicity observed. We discuss the putative role of MTX pharmacogenetics in the pathogenesis of MTX-NT.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Ácido Fólico/metabolismo , Metotrexato/efectos adversos , Síndromes de Neurotoxicidad/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Antimetabolitos Antineoplásicos/uso terapéutico , Preescolar , Femenino , Ácido Fólico/genética , Humanos , Imagen por Resonancia Magnética , Metotrexato/uso terapéutico , Síndromes de Neurotoxicidad/genética , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoAsunto(s)
Opacidad de la Córnea/tratamiento farmacológico , Iduronidasa/uso terapéutico , Mucopolisacaridosis I/tratamiento farmacológico , Mucopolisacaridosis I/fisiopatología , Trastornos de la Visión/tratamiento farmacológico , Adulto , Opacidad de la Córnea/genética , Opacidad de la Córnea/fisiopatología , Humanos , Masculino , Mucopolisacaridosis I/genética , Proteínas Recombinantes/uso terapéutico , Trastornos de la Visión/genética , Trastornos de la Visión/fisiopatología , Agudeza Visual/efectos de los fármacosRESUMEN
We present a 3-year-old boy affected with Hunter syndrome. When we first evaluated the patient glycosaminoglycans (GAG) in urine were elevated (94.6 ng/nmol/creatinine); the enzyme activity determined in serum was decreased (3.9 nmol/hxml) and the mutation found was N350H, exon 8. His clinical signs were coarse facial features, hepatomegaly (6 cm), splenomegaly (6 cm), elbow stiffness and hypospadias; dilatation of the perivascular spaces and white matter abnormalities, mitral regurgitation. After two weeks on enzyme replacement therapy (ERT) with idursulfase (IDS), the excretion of GAG was decreased to 36.2 ng/nmol/creatinine and the liver and spleen volumes were reduced to normal limits. He was subsequently noted to have a softer, finer skin, he had no further bouts of bronchitis, and his physical activity improved. This indicates that IDS in young children is well tolerated and that it has several effects which may confer clinical benefits with long-term therapy.
Asunto(s)
Iduronato Sulfatasa/uso terapéutico , Mucopolisacaridosis II/tratamiento farmacológico , Preescolar , Humanos , MasculinoRESUMEN
Alexander disease is a neurodegenerative disorder characterized by macrocephaly and progressive demyelination with frontal lobe preponderance. The infantile form, the most frequent variant, appears between birth and 2 years of age and involves a severe course with a rapid neurologic deterioration. Although magnetic resonance imaging is useful for diagnosis, currently diagnosis is confirmed by the finding of missense mutation in the glial fibrillary acidic protein (GFAP) gene. This case reports a female who presented at the age of 5 months with refractory epilepsy and hypotonia. Laboratory examinations, muscle biopsy examination, and energetic metabolic study in muscle indicated increased concentrations of lactate, mitochondria with structural abnormalities, and decreased cytochrome-c oxidase activity respectively. Later, both clinical course and magnetic resonance findings were compatible with Alexander disease, which was confirmed by the finding of a novel glial fibrillary acidic protein gene mutation.